Scientific Serendipity: Malaria Protein Part of a Promising New Cancer Treatment

by Daniel Sokolowski

COPENHAGEN, Denmark— “Believe it or not, there is no such thing as ‘a cure for cancer.’ Cancers afflict different organs and cell types, and are caused by different carcinogens and types of mutations. As a result, each case of cancer has very different characteristics, and requires unique treatment plans. The idea that there is a single, yet-to-be-discovered treatment that effectively cures every single form of cancer is misleading and gives the public an oversimplified view of cancer’s complexity.”

This is a typical rant that one’s pessimistic, know-it-all pre-med friends like to bring up at parties whenever somebody casually mentions how they wish that somebody would cure cancer already. Fortunately, as a sharp rebuttal to medical pedants everywhere, such an “impossible” broad-spectrum cancer treatment is already being researched.

The idea for the treatment in question was first developed in October 2015 by Danish scientists at the University of Copenhagen. Professor Ali Salanti and his team were developing and testing a vaccine—not for cancer, but for malaria, to be given to pregnant women.

When a malaria parasite replicates inside an infected red blood cell, it creates a special anchor protein on the outside of the cell, called VAR2CSA, which attaches itself—like Velcro, but much stronger— to a specific receptor on the walls of the victim’s blood vessels. That way, the cell and its parasite cling to the vessel walls and stay out of circulation, avoiding detection and eradication from white blood cells. The receptor found in pregnant women that VAR2CSA binds to is a polysaccharide (sugar) on the interior of placental blood vessels called chondroitin sulfate A (CSA), which is important for rapid cell replication and the development of blood vessels. It was this VAR2CSA-CSA binding that Salanti’s research group was attempting to prevent, among other malarial infection factors, with their malaria vaccine.

During their research, Salanti and his team realized something important about the rapid-growth CSA sugar—it is also found in cancer cells. “For decades,” Salanti says, “scientists have been searching for similarities between the [rapid] growth of a placenta and a tumor.” Intrigued that CSA might be the answer to this hot research topic in the oncological community, Salanti asked his former student Mads Daugaard, now a cancer researcher at the University of British Columbia, to confirm his idea. He was indeed right, and was on to something great.

Salanti’s team, in collaboration with Daugaard and his team of researchers, discovered that VAR2CSA could effectively deliver drugs to cancer cells and serve as a vital component for a new kind of cancer treatment. The researchers theorized that VAR2CSA molecules would bind to the CSA in tumors, similar to how VAR2CSA binds to CSA in placentas. The tumors, in turn, would then absorb the attached VAR2CSA molecules. Since tumors contain CSA, and healthy, non-placental tissues do not, the VAR2CSA could be used to track down and deliver drugs to cancer cells hidden among normal, healthy cells. To test their theory, Daugaard and Salanti’s groups tested VAR2CSA’s drug delivery ability on thousands of samples of several different cancer types. The results of this initial testing showed that VAR2CSA is absorbed by more than 90 percent of all tumor categories.

The next step in the research was to make VAR2CSA “poisonous” to the cancer cells that ingest it. They achieved this by fusing VAR2CSA molecules to toxins derived from diphtheria (a serious bacterial infection). As a result, when tumors absorb the poisoned, but still functional VAR2CSA proteins, they were weakened and their growth was halted. What makes this VAR2CSA protein-toxin combination so promising as a cancer treatment is that it exclusively attacks tissues that contain CSA, tumors and placentas, and does not significantly harm other healthy tissue. This localization of treatment is a significant step up from standard chemotherapies, which damage both normal and cancer cells alike in the hope that the cancer dies before the patient does.

The researchers tested their new protein-toxin compound on mice implanted with human tumors. One group of mice received non-Hodgkin’s lymphoma, another got prostate cancer and a third was afflicted with metastatic bone cancer. Half the mice in each group were injected with one dose of treatment, while the other half received no treatment. The experiment was quite successful. In the lymphoma group, the tumors of the treated group were only a quarter of the size of the tumors of the control group. In the cohort with prostate cancer, tumors disappeared in a third of the treated mice. Lastly, in the bone cancer group, five out of the six treated mice were still alive almost eight weeks after treatment. In comparison, all of the mice in the bone cancer control group died by this time. In further testing on other mice implanted with tumors, three doses of protein-toxin halted tumor growth, and even caused tumors to shrink.

Based on the results of these animal studies, Salanti and Daugaard’s malaria-based cancer treatment has the potential to greatly increase many cancer patients’ chances of survival. However, there are some drawbacks to this treatment. For one, the therapy is broad-spectrum, but not universal. So, even though the protein-toxin effectively attacks 90 percent of all tumor types, that leaves nearly 10 percent for which the treatment would have no significant effect. Another drawback centers around placental tissue containing CSA. So, pregnant women would not and should not receive this treatment, since the protein-toxin molecules would bind to and damage the woman’s placenta, jeopardizing the health of both the mother and her unborn baby. On top of all this, the treatment is still in the prototype stage, and due to strict medical testing standards, human trials of the malarial cancer treatment cannot start until at least four years from now.

This new, broad-spectrum cancer treatment, with all its current imperfections, still has a long way to go before it starts saving human lives. The treatment is effective in mice, but it is unknown what effect this malarial cancer treatment might have on larger and more complex humans. It could have little-to-no effect, or cause horrible side effects. No one can know for sure until proper human testing is done.

For now, hold out hope that the treatment will work, and that cancer may soon become a thing of past— no matter what your buzzkill medicine-nerd friends tell you.